6e5g
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of human TEAD2-Yap binding domain covalently bound to an allosteric regulator== | |
| + | <StructureSection load='6e5g' size='340' side='right'caption='[[6e5g]], [[Resolution|resolution]] 2.43Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6e5g]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E5G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6E5G FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.43Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HUY:1-(2-{[3-(trifluoromethyl)phenyl]amino}phenyl)ethan-1-one'>HUY</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6e5g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e5g OCA], [https://pdbe.org/6e5g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6e5g RCSB], [https://www.ebi.ac.uk/pdbsum/6e5g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6e5g ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The Hippo pathway coordinates extracellular signals onto the control of tissue homeostasis and organ size. Hippo signaling primarily regulates the ability of Yap1 to bind and co-activate TEA domain (TEAD) transcription factors. Yap1 tightly binds to TEAD4 via a large flat interface, making the development of small-molecule orthosteric inhibitors highly challenging. Here, we report small-molecule TEADYap inhibitors that rapidly and selectively form a covalent bond with a conserved cysteine located within the unique deep hydrophobic palmitate-binding pocket of TEADs. Inhibition of TEAD4 binding to Yap1 by these compounds was irreversible and occurred on a longer time scale. In mammalian cells, the compounds formed a covalent complex with TEAD4, inhibited its binding to Yap1, blocked its transcriptional activity, and suppressed expression of connective tissue growth factor. The compounds inhibited cell viability of patient-derived glioblastoma spheroids, making them suitable as chemical probes to explore Hippo signaling in cancer. | ||
| - | + | Small-Molecule Covalent Modification of Conserved Cysteine Leads to Allosteric Inhibition of the TEADYap Protein-Protein Interaction.,Bum-Erdene K, Zhou D, Gonzalez-Gutierrez G, Ghozayel MK, Si Y, Xu D, Shannon HE, Bailey BJ, Corson TW, Pollok KE, Wells CD, Meroueh SO Cell Chem Biol. 2018 Dec 18. pii: S2451-9456(18)30432-X. doi:, 10.1016/j.chembiol.2018.11.010. PMID:30581134<ref>PMID:30581134</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6e5g" style="background-color:#fffaf0;"></div> |
| - | [[Category: Bum-Erdene | + | == References == |
| - | [[Category: Gonzalez-Gutierrez | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Bum-Erdene K]] | ||
| + | [[Category: Gonzalez-Gutierrez G]] | ||
| + | [[Category: Meroueh SO]] | ||
Current revision
Crystal structure of human TEAD2-Yap binding domain covalently bound to an allosteric regulator
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